Abstract 6503: A case of stage IIA anal squamous cell carcinoma (SCC) diagnosed using a multi-cancer early detection (MCED) test
Authors: David A. Myers, Brenda Wood
Journal: Cancer Research (2023)

Abstract Although some anal cancers can be detected early via screening, current screening options have limitations. A blood-based MCED test that uses a cell-free DNA-based targeted methylation assay and machine learning classifiers to detect a cancer signal and predict the cancer signal origin (CSO) is available for cancer screening. If the MCED test detects a cancer signal, the test reports ‘cancer signal detected’ with 1 or 2 CSO prediction(s). In the Circulating Cell-free Genome Atlas (CCGA) study, the top-predicted CSO was 89% accurate overall. Despite high average CSO prediction accuracy, the biological similarity among HPV-related cancers of the anogenital tract, and head and neck (H&amp;N), may lead to CSO misclassification. An HPV-driven anal cancer case is reported to review the diagnostic journey following a positive test result and misclassified CSO prediction. An asymptomatic 67-year-old White, non-Hispanic female (BMI: 21.6 kg/m2) with history of HPV-associated cervical dysplasia and resultant hysterectomy &amp;gt;20 years prior was screened using the MCED test. She had an anoscopy 2 years prior to using the test for hemorrhoids. 11 days after a blood sample was collected for analysis, a positive test result (CSO1=Lung; CSO2=H&amp;N) was communicated to the patient (Day 1). Chest CT w/o contrast was normal except for a small pericardial effusion (Day 2). The patient was referred to an ENT specialist for an extensive evaluation; there was no evidence of cancer found (Day 7). Repeat chest CT with and w/o contrast and with 2mm cuts was also normal except for the small pericardial effusion (Day 21). After the initial diagnostic workup ended, the possibility of HPV-driven CSO misclassification was raised, and in the context of past medical history, HPV-driven anorectal cancer was considered. The patient underwent a flex sigmoidoscopy, which revealed a 4 cm anterior distal anorectal mass consistent with cancer (Day 60). Biopsy showed invasive moderately differentiated SCC with focal keratinization and negative for lymphovascular invasion (Day 65). PET (skull base to mid-thigh) showed a 1.8 cm focus of activity in the anorectal area and no evidence of metastatic disease (Day 71). MRI of the pelvis with and w/o contrast showed a 2.7 cm anal mass with no lymph node invasion consistent with T2N0 disease (Day 72). Consultation with a radiation oncologist diagnosed the cancer as p16+, cT2N0M0 (stage IIA) SCC of the anal canal (Day 72). She was provided chemoradiation for ~1.5 months (Day 80). The most recent scans revealed no evidence of cancer (Day 364). The MCED test detected a cancer signal for an asymptomatic individual with stage IIA anal cancer. In the CCGA study, sensitivity was 75% in stage II anal cancer. Based on this case, CSO misclassification may be considered in patients with an HPV medical history. The use of this MCED test informed aggressive cancer workup and led to early detection and treatment with curative intent. Citation Format: David A. Myers, Brenda Wood. A case of stage IIA anal squamous cell carcinoma (SCC) diagnosed using a multi-cancer early detection (MCED) test [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6503.